Dietary supplements for treating inflammation-related diseases

ABSTRACT

The present invention provides dietary supplements, medical foods and methods effective to ameliorate at least one of the symptoms, preferably all of the symptoms, of an inflammation-related disease. The dietary supplements of the present invention include rosemary, curcumin and at least one component selected from the group consisting of quercetin and rutin. The medical foods of the present invention include include rosemary and at least one component selected from the group consisting of curcumin, quercetin and rutin. The medical foods of the present invention also include macronutrients. The methods of the present invention include the step of administering to a person suffering from an inflammation-related disease an effective amount of a dietary supplement or medical food of the present invention.

FIELD OF THE INVENTION

[0001] The present invention relates to dietary supplements and medicalfoods for treating inflammation-related diseases. The compositions ofthe present invention include rosemary.

BACKGROUND OF THE INVENTION

[0002] In 1948, the World Health Organization defined health as not onlythe absence of disease, but also the presence of physical, mental, andsocial well-being. (Constitution of the World Health Organization. In:World Health Organization, Handbook of Basic Documents. 5th ed. Geneva:Palais des Nations, 3-20 (1952)). The status of a patient's physical,mental, and social functioning is often referred to in the literature asquality-of-life and is used as a measure of health outcome. In the past25 years, there has been a nearly exponential increase in the evaluationof quality-of-life as a technique of clinical research as a component ofdetermining clinical benefit from an intervention protocol. For example,in 1973, only five articles listed quality-of-life as a key word in theMedline database, whereas in the subsequent four years there weresuccessively 195, 273, 490, and 1,252 such articles. (Testa MA andSimonson DC, N Eng J Med. 334:835-840 (1996). In 1998, approximately3,724 articles listed quality-of-life as a key word. Thus, the healthoutcome, or quality-of-life, associated with a clinical intervention hasbeen recognized as an important tool in measuring effectiveness andcosts of medical care. (Wilson IB and Cleary PD., JAMA., 273:59-65(1995)).

[0003] Extensive research has resulted in the development of instrumentsthat measure health outcome using quality-of-life tools that followacademically well-established and statistically validated psychometricprinciples. (Ware JE Jr., J Chronic Dis., 40:473-480 (1987); Spilker B.,Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd ed.Philadelphia, Pa.: Lippincott-Raven Co; 1995.) One such tool is theSF-36 (Short form-36), which has been widely used in clinical trials andin clinical practice to assess health outcome. (Clancy CM and EisenbergJM, Science, 282:245-246 (1998)). The SF-36 was derived from the MedicalOutcomes Study, which involved 11,336 patients from 523 differentclinical sites. (Ware JE, Sherbourne CD, Davies AR. Developing andtesting the MOS 20-item short-form health survey. In: Stewart AL andWare JE, eds., Measuring functioning and well-being: The MedicalOutcomes Study approach. Durham, N.C.: University Press, 277-290 (1992);Ware JE. SF-36 Health Survey: manual and interpretation guide. Boston,Mass.: Nimrod Press; 2:1-3:22 (1993)). The validity and reliability ofthe SF-36 has been proven in several studies in which researchers testedinternal consistency, within subject reliability, and differentiationbetween patient populations. (McHorney CA, et al., Medical Care,31:247-263 (1993); McHorney CA, et al., Medical Care, 30:S253-S265(1992); Jenkinson C, et al., Br Med J, 306:1436-1440 (1993); Brazier JE,et al., Br Med J 305:160-164 (1992)). The SF-36 has been shown topredict the course of depression during a two-year study, and to belower overall in patients who experience chronic health disorders.(Wells KB, et al., Archives General Psychiatry, 49:788-794 (1992);Schlenk EA, et al., Quality of Life Res., 7:57-65 (1998)).

[0004] The SF-36 is a 36-item questionnaire that assesses eightdimensions of health outcome: physical functioning, role-physical,bodily pain, general health, vitality, social functioning,role-emotional, and mental health. Results from the questionnaire can bereported as a relative number on a scale of 0 to 100, in which 100 isthe highest or most functional and 0 is the most compromised for thatcategory of functioning. A summary of the meaning of high and low scoresfor each category is shown in Table 1. TABLE 1 Description of Very Highand Very Low Scores for the Eight Categories of the MOS SF-36Questionnaire. SF-36 Interpretation Interpretation Category of a LowScore of a High Score Physical Limited in performing all Performs alltypes of physical Functioning physical activities activities includingthe most (PF) including bathing or vigorous without limitations duedressing due to health to health Role- Problems with work or No problemswith work or other Physical other daily activities as a daily activitiesas a result of (RP) result of physical health physical health BodilyVery severe and No pain or limitations due to Pain (BP) extremelylimiting pain pain General Evaluates personal health Evaluates personalhealth as Health (GH) as poor and believes it is likely to get worseexcellent Vitality Feels tired and worn out Feels full of pep and energy(VT) all of the time all of the time Social Extreme and frequentPerforms normal social activities Functioning interference with normalwithout interference due to (SF) social activities due physical oremotional problems to physical or emotional problems Role- Problems withwork or No problems with work or other Emotional other daily activitiesas a daily activities as a result of (RE) result of emotional emotionalproblems problems Mental Feelings of nervousness Feels peaceful, happy,and calm Health (MH) and depression all of the all of the time time

[0005] The latter half of the twentieth century has been characterizedby an increasing prevalence of chronic disorders. Indeed, seven of theten leading causes of death in the USA are chronic in nature, accountingfor 72% of the deaths from all causes. (National Center for HealthStatistics. Health, United States, 1995. Hyattsville, Md.: Public HealthService, 1995.) Chronic disorders such as rheumatic disorders, chronicpain, and fatigue contribute to the 6% of the population that isimpaired to some extent in the conduct of major life activities such aswork, school, and self-care. (US Department of Health and HumanServices, Public Health Service. Healthy People 2000: National HealthPromotion and Disease Prevention Objectives. Hyattsville, Md.: PublicHealth Service; 1991.) Health care use also appears to be substantialfor patients with chronic conditions.

[0006] In chronic conditions such as rheumatic disorders and chronicpain, biological and physiological factors have an inconsistentrelationship to symptoms. (Wilson IB, Cleary PD., JAMA, 273:59-65(1995)). Therefore, they are difficult to measure by laboratory values.In fact, in clinical practice, anywhere from 30% to 80% of patients whosee a physician may have conditions for which no physiological ororganic cause is found after routine investigation. (Wilson IB andCleary PD, JAMA, 273:59-65 (1995)).

[0007] In these chronic conditions, pain and fatigue are often sufferedover many years without correlation to a diagnosable or definable acuteor chronic disease. Therefore, without anatomical or physicalcorrelation, a patient's response to therapy must be monitored bymeasuring the level of symptoms they report over a period of time. TheMOS SF-36 questionnaire is particularly suited to this type of analysis.For example, patients with chronic disorders have been reported to scorelower than the norm in several categories of the MOS SF-36, includingbodily pain, role-physical, role-emotional, and vitality. See, e.g.,Ware JE., SF-36 Health Survey: manual and interpretation guide. Boston,Mass.: Nimrod Press; 2:1-3:22 (1993); Schlenk EA, et al., Health-relatedquality of life in chronic disorders: a comparison across studies usingthe MOS SF-36, Quality Life Research, 7:57-65 (1998)).

[0008] Although similarities in different categories of the MOS can beobserved, data from patients who experience chronic conditions suggeststhat these patients may show higher variability when analyzingindividual MOS categories than with the PCS and MCS summary scores. Thisvariability may result from the frequent coexistence of chronicconditions.

[0009] Taking these considerations into accounts, Ware et al. have usedprincipal component analysis on the MOS SF-36 data collected from 2,474subjects from the US general population to derive summary scores for theeight categories shown above. (Ware JE Jr., Kosinski M, Keller SD. SF-36Physical & Mental Health Summary Scales: A user's manual. Boston, Mass.:The Health Institute, New England Medical Center; 3:1-4:6 (1994)). ThePhysical Component Summary (PCS) and Mental Component Summary (MCS)provide two reliable, reproducible scores for the physical and mentalhealth, respectively. The PCS and MCS scores are converted to a scale of0 to 100, in which 50 is the mean for the US population.

[0010] This analysis of the MOS data takes into account the range ofsymptoms seen with the chronic condition and reduces the variabilityfrom individual patient differences. Low scores on the PCS indicatesubstantial limitations in self care, physical, social, and roleactivities, severe bodily pain, frequent tiredness, and health generallyrated as poor, whereas high scores indicate no physical limitations,high energy level, and health generally rated as excellent. Low scoreson the MCS indicate frequent psychological distress, substantial socialand role disability due to emotional problems, and/or health generallyrated as poor, whereas high scores indicate frequent positive affect andabsence of psychological distress and limitations in usual social androle activities. Table 2 shows relative PCS and MCS scores for variouschronic health conditions as compared to US population normative data.Standard deviation is abbreviated as S.D. TABLE 2 Comparison of PhysicalComponent Summary (PCS) and Mental Component Summary (MCS) of the MOSSF-36 Questionnaire. Number of Mean PCS Mean MCS Norms for US PopulationRespondents Score (sd) Score (sd) Females 1,412 49.07 (10.42) 49.33(10.32) Males 1,055 51.05  (9.39) 50.73  (9.57) “Healthy” individuals  465 55.26  (5.10) 53.43  (6.33) with no chronic conditions from USpopulation Individuals with self-   881 47.92 (11.62) 43.46 (11.42)reported depression symptoms Individuals with Clinical   502 44.96(12.05) 34.84 (12.17) Depression Individuals with Arthritis   826 43.15(11.62) 48.81 (11.11) Individuals reporting   519 43.14 (11.56) 46.88(11.73) chronic back pain Individuals reporting   818 47.44 (10.81)48.23 (10.74) allergies Individuals with   214 46.88 (11.49) 46.16(12.06) dermatitis or chronic skin rash

[0011] It has been the experience of the present inventors that manypatients with inflammation-related diseases respond with only moderateimprovement to dietary programs. Further, this response has beenvariable, with a large percentage of patients with inflammation-relateddiseases not responding to dietary changes at all. Pharmaceuticalapproaches, such as non-steroidal anti-inflammatories oranti-depressants have been used with some success, but many of thesedrugs carry the risk of undesirable side-effects.

[0012] Consequently, there is a need for a dietary supplement and/ormedical food that ameliorates at least one of the symptoms, preferablyall of the symptoms of an inflammation-related disease, such asarthritis and inflammatory bowel disease. In particular, there is a needfor a dietary supplement and/or medical food that improves both thephysical and mental functioning of a person suffering from aninflammation-related disease, such as arthritis and inflammatory boweldisease.

SUMMARY OF THE INVENTION

[0013] The present invention provides dietary supplements, medical foodsand methods effective to ameliorate at least one of the symptoms,preferably all of the symptoms, of an inflammation-related disease, suchas arthritis and inflammatory bowel disease. Preferred dietarysupplements and medical foods of the present invention improve both thephysical and mental functioning of a person suffering from aninflammation-related disease, such as arthritis and inflammatory boweldisease.

[0014] The dietary supplements of the present invention are compoundedfor the amelioration of an inflammation-related disease and includerosemary, curcumin and at least one component selected from the groupconsisting of quercetin and rutin. A presently preferred dietarysupplement of the invention includes rosemary, curcumin and quercetin. Adaily dose of the dietary supplements of the present invention includerosemary in an amount of from about 180 mg to about 220 mg; curcumin inan amount of from about 360 mg to about 440 mg; quercetin, if utilized,in an amount of from about 360 mg to about 440 mg; and rutin, ifutilized, in an amount of about 360 mg to about 440 mg.

[0015] Additionally, presently preferred dietary supplements of theinvention may include at least one component selected from the groupconsisting of limonene, preferably D-limonene, hesperidin and ginger. Adaily dose of the dietary supplements of the present invention includelimonene, if utilized, in an amount of from about 180 mg to about 220mg; hesperidin, if utilized, in an amount of from about 360 mg to about440 mg; and ginger, if utilized, in an amount of from about 180 mg toabout 220 mg. The dietary supplements of the present inventionoptionally include at least one vitamin and at least one non-vitaminantioxidant.

[0016] The present invention also provides medical foods comprisingrosemary, at least one macronutrient selected from the group consistingof protein, carbohydrate and fat, and at least one member of the groupconsisting of quercetin, curcumin and rutin, the medical food beingcompounded for the amelioration of an inflammation-related disease. Adaily dose of the medical foods of the present invention includerosemary in an amount of from about 180 mg to about 220 mg; curcumin, ifutilized, in an amount of from about 360 mg to about 440 mg; quercetin,if utilized, in an amount of from about 360 mg to about 440 mg; andrutin, if utilized, in an amount of about 360 mg to about 440 mg.

[0017] Additionally, presently preferred medical foods of the inventionmay include at least one component selected from the group consisting oflimonene, preferably D-limonene, hesperidin and ginger. A daily dose ofthe medical foods of the present invention include limonene, ifutilized, in an amount of from about 180 mg to about 220 mg; hesperidin,if utilized, in an amount of from about 360 mg to about 440 mg; andginger, if utilized, in an amount of from about 180 mg to about 220 mg.The medical foods of the present invention optionally include at leastone vitamin and at least one non-vitamin antioxidant.

[0018] The medical foods of the present invention also includemacronutrients. Macronutrients included in the medical foods of thepresent invention include protein, carbohydrates and fat. The protein ispreferably obtained from a cereal grain that is gluten-free, orsubstantially gluten-free. The presently preferred protein source is ahypoallergenic rice protein concentrate, suitably prepared as disclosedin U.S. patent Ser. No. 4,876,096, incorporated herein by reference. Adaily dose of the medical foods of the present invention include proteinin an amount of from about 25 g to about 35 g. Carbohydrates areprovided as rice fiber, bran and/or flour, or equivalent gluten-free orsubstantially gluten-free grain fiber, bran and/or flour. Carbohydratecan also be provided as rice syrup solids which contain approximately 70to 90 percent by weight of high molecular weight dextran, or asequivalent gluten-free or substantially gluten-free grain syrup solids.A daily dose of the medical foods of the present invention includecarbohydrate in an amount of from about 43 g to about 69 g. Fats arepreferably provided as medium chain triglycerides, preferably incombination with canola oil. Canola oil can be substituted withnutritionally equivalent oils, such as flaxseed oil and safflower oil.Medium chain triglycerides useful in the compositions of the presentinvention include a fatty acid moiety having an 8 to 14 carbon atombackbone, and can be derived from, for example, coconut oil and relatedtropical oils. A daily dose of the medical foods of the presentinvention include fats in an amount of from about 3 g to about 8 g.

[0019] Presently preferred medical foods of the invention may alsoinclude at least one vitamin, or vitamin precursor. Preferred vitaminspossess antioxidant properties and include vitamins A, C and E, and/ortheir biochemical precursors. Presently preferred medical foods of theinvention also include at least one trace element, preferably selectedfrom the group consisting of zinc, manganese and selenium. Presentlypreferred medical foods of the invention also may include at least oneadditional antioxidant selected from the group consisting ofcarotenoids, N-acetylcysteine and L-glutamine. The presently preferredamounts of preferred vitamins, trace elements, non-vitamin antioxidantsand other components that can be included in the medical foods of theinvention are set forth in Table 3.

[0020] In addition, the present invention provides methods for treatinginflammation-related diseases. In one embodiment, the methods of thepresent invention include the step of administering to a personsuffering from an inflammation-related disease an effective amount of adietary supplement of the present invention. Preferably the dietarysupplement is administered at least once per day. In another embodiment,the methods of the present invention include the step of administeringto a person suffering from an inflammation-related disease an effectiveamount of a medical food of the present invention. Preferably themedical food is administered at least once per day.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0021] The present invention provides dietary supplements, medical foodsand methods effective to ameliorate at least one of the symptoms of aninflammation-related disease. Preferred dietary supplements and medicalfoods of the present invention improve both the physical and mentalfunctioning of a person suffering from an inflammation-related disease.As used herein, the term “inflammation-related disease” refers to adisease for which inflammation is a predominant symptom. By way ofnon-limiting example, the term “inflammation-related disease” includesarthritis (including osteoarthritis and rheumatoid arthritis),inflammatory bowel disease, eczema, psoriasis, atopic dermatitis,psoriatic arthropathy and asthma.

[0022] The compositions of the present invention include rosemary,curcumin (always present in the dietary supplements and optionallypresent in the medical foods) and at least one component selected fromthe group consisting of quercetin and rutin. Preferably rosemary isutilized as an extract of ground rosemary leaves; curcumin is utilizedas a tumeric extract in powder form; quercetin is utilized as eitherpure quercetin or as a quercetin glycoside (e.g., rutin). The dietarysupplements of the present invention may preferably include ginger,limonene and hesperidin. Ginger is preferably utilized as a concentrateof a ginger root extract. Any substantially pure preparation of limoneneor hesperidin can be utilized in the compositions of the presentinvention.

[0023] Rosemary contains the flavonoids carnosol, carnosic acid,rosmanol and ursolic acid and the compositions of the present inventioncan be supplemented with one or more of the foregoing flavonoids. Gingercontains the potent antioxidant 6-gingerol, together with zingerone and6-shogaol. The compositions of the present invention can be supplementedwith one or more of the foregoing ginger components.

[0024] The present invention also provides medical foods comprisingrosemary, at least one macronutrient selected from the group consistingof protein, carbohydrate and fat, and at least one member of the groupconsisting of quercetin, curcumin and rutin, the medical food beingcompounded for the amelioration of an inflammation-related disease. Theprotein source is preferably a hypoallergenic rice protein extract,suitably prepared as described in U.S. patent Ser. No. 4,876,096,incorporated herein by reference. The hypoallergenic rice proteinextract is preferably fortified with at least one of the following aminoacids: L-lysine, L-threonine and L-cysteine. In a presently preferredembodiment, the medical foods of the present invention are fortifiedwith L-lysine and L-threonine in amounts of 6.3% and 0.28% of the weightof rice protein, respectively.

[0025] Both the dietary supplements and medical foods of the presentinvention are preferably used in powder form which can be dissolved in aliquid suitable for human consumption, such as water or a fruit juice.The dietary supplements and medical foods of the present invention can,however, be utilized in any suitable form, such as a solid bar, as apaste, gel, tablet, capsule or liquid.

[0026] Typically, the dietary supplements and medical foods of thepresent invention are preferably administered two times per day,preferably once in the morning and once in the afternoon. A typicaltreatment regime for the dietary supplements or medical foods willcontinue for four to eight weeks. Depending on such factors as themedical condition being treated and the response of the patient, thetreatment regime may be extended. A medical food of the presentinvention will typically be consumed in two servings per day as either ameal replacement or as a snack between meals. A serving size for amedical food of the present invention will preferably be in the range offrom about 45 grams to about 60 grams and will provide from about 180calories to about 220 calories to the consumer. In a presently preferredtreatment regime a person in need of treatment is provided with twoservings of a medical food of the present invention per day. A presentlypreferred serving size is about 52 grams of powdered medical food whichdelivers about 200 calories to the consumer.

[0027] Suitable ranges for each component preferably included in amedical food in accordance with the present invention are set forth inTable 3 of Example 1. For a dietary supplement compounded in accordancewith the present invention, the same ranges of specific ingredients tobe included(e.g. Rosemary, Curcurmin, Quercetin, etc.) are utilized. Thefollowing examples merely illustrate a preferred embodiment nowcontemplated for practicing the invention, but should not be construedto limit the invention.

EXAMPLE 1 Improvement in PCS and MCS Components of the MOS SF-36 inPatients Treated with a Preferred Medical Food of the Present Invention

[0028] Control Subjects: Sixteen subjects were included in the control,no-intervention study. These subjects were asked to complete a MOSquestionnaire at the beginning of the study, and subsequently after aninterval of between 1 to 15 weeks. Subjects were told to maintain theirroutines of diet, medication, and lifestyle and make no intentionalchanges in the intervening time. The control subjects varied in age from39 to 61 years, with an average age of 49±7 years, and included 4 menand 12 women.

[0029] Subjects with inflammation-related conditions: Fourteen patientswith primary symptoms relating to chronic inflammation were evaluatedwith the intervention protocol for response. Subjects varied in age from16 to 55 years, with an average age of 43±11 years, and included 5 menand 12 females.

[0030] Intervention Protocol: Control subjects received no intervention.Nutritional intervention for the subjects with inflammation-relateddisease involved supplementation of the daily diet with a presentlypreferred medical food of the invention described in Table 3(Composition 1). Composition 1 was manufactured as a powdered drink mix,which was prepared by each subject at the time of use by mixing theappropriate amount of the composition in either water or a juice of thesubject's choosing. Composition 1 was delivered in two servings per dayof 52-gram size, which delivered 400 calories per day to the diet.

[0031] Intervention Protocol with Clinical Assessment: Subjects on theintervention protocols were provided with Composition 1 in a powderedform and a dietary protocol. The dietary changes prescribed in thedietary protocol consisted of a modified elimination diet, which isdescribed as a diet free of substances known to produce allergenicresponses and is preferably vegetarian. Subjects were instructed to makeno changes in supplementation, medication, or exercise routine duringthe course of the intervention. Medications consumed by the subjectswere documented at each office visit. Likewise, compliance to theprotocol during the previous weeks was documented by questionnaireduring the office visit.

[0032] Subjects were maintained on the protocol for between four andnine weeks. Subjects were evaluated by the MOS SF-36 questionnaire, acondition-specific questionnaire when appropriate, and a questionnaireto evaluate general physical symptoms called the Medical SymptomsQuestionnaire (MSQ), described in Bland, J. S., and Bralley, J. A.,Journal of Applied Nutrition 44: 2-15 (1992). Data were analyzed bystandard statistical methods. TABLE 3 Weight ranges for components ofmedical food of the invention and composition of presently preferredmedical food of the invention (Composition 1). Amount per day in medicalfood of the present invention Nutrient Units Composition 1 Range Riceprotein grams 30 25-35 Rice fiber grams 8 7-9 Rice carbohydrates grams48 43-53 Vegetable Oil grams 3.34 3-4 Medium-chain tryglycerides grams3.34 3-4 Vitamin A IU 10,000  9,000-11,000 (mixed carotenoids/palmitate)Vitamin C mg 360 320-400 Calcium mg 550 500-600 Vitamin D IU 200 180-220Vitamin E IU 200 180-220 Thiamin (B1) mg 4 3-5 Riboflavin (B2) mg 4 3-5Niacin (B3) mg 70 60-80 Vitamin B6 mg 10  8-12 Folic acid pg 160 140-180Vitamin B12 mcg 6 5-7 Biotin mcg 300 270-330 Pantothenic Acid mg 10 8-12 Phosphorous mg 400 360-440 Magnesium mg 560 500-600 Zinc mg 2018-22 Selenium mcg 150 140-160 Copper mg 2 1.5-2.5 Manganese mg 43.5-4.5 Chromium mcg 120 100-140 N-acetyl cysteine (NAC) mg 200 180-220Sodium sulfate mg 100  80-120 Molybdenum mcg 76 65-85 L-glutamine mg1500 1200-1800 L-threonine mg 68 60-75 L-lysine HCl mg 1540 1200-1800Citrulline mg 200 180-220 Hesperidin mg 400 360-440 Quercetin mg 400360-440 Rutin mg 400 360-440 Curcumin mg 400 360-440 Rosemary mg 200180-220 D-limonene mg 200 180-220 Ginger mg 200 180-220

[0033] Changes with no intervention: The changes in MOS SF-36 responseswas evaluated over time with no intervention. In Table 4, the averagechange in score in the eight MOS categories is seen to be seven or lesspoints in the 16 control subjects. In Table 5, the summary PCS and MCSscores for the control subjects are shown, which also reveal that thesummary scores remain consistent over the course of 4±3 weeks. TABLE 4Summary of the Eight Categories of the SF-36 in 16 Subjects With noIntervention (Average Intervening Time Between Initial Score and FinalScore Was 4 ± 3 Weeks). Average Initial Score Final Score Change inScore Physical Functioning 60 ± 30 64 ± 32 −4 ± 17 Role-Physical 41 ± 3944 ± 40 −3 ± 38 Bodily Pain 55 ± 21 50 ± 26   5 ± 21 General Health 54 ±24 50 ± 21   4 ± 16 Vitality 31 ± 19 38 ± 15 −7 ± 11 Social Function 66± 27 62 ± 24   4 ± 26 Role-Emotional 53 ± 43 51 ± 43   2 ± 42 MentalHealth 60 ± 20 64 ± 11 −4 ± 18

[0034] TABLE 5 Physical Component Summary (PCS) and Mental ComponentSummary (MCS) Scores From the MOS SF-36 in 16 Subjects With noIntervention (Average Intervening Time Was 4 ± 3 Weeks). PhysicalComponent Mental Component Summary (PCS) Summary (MCS) Initial FinalInitial Final Score Score Change Score Score Change Average 39 ± 11 39 ±13 0.34 ± 7.9 43 ± 13 42 ± 8.4 0.51 ± 9.9 (sd)

[0035] Data obtained from 14 subjects with inflammation-relatedconditions who received the nutritional intervention are shown below. InTable 6, the average change per individual category of the MOS SF-36 isshown. In Table 7, the primary complaint(s) and weeks on the protocolare shown, as well as the PCS and MCS scores.

[0036] After intervention with Composition 1, the majority of subjectsreported improvement in the physical parameters of the MOS SF-36, asshown by the increase in scores in the Physical Functioning, RolePhysical, Bodily Pain, and General Health sections. The increase inscores for the majority of patients is reflected in the PhysicalComponent Summary score, shown in Table 7. Two patients reportedsignificant increase in symptoms, although both patients showedconsiderable improvement on the Mental Component Summary scores. Withoutthese two subjects included, the average improvement in PCS is 5 points.TABLE 6 Summary of the 8 Categories of the MOS SF-36 in 14 Subjects WithInflammation-Related Conditions Average Initial Score Final Score Changein Score Physical Functioning 69 ± 32 75 ± 33  6 ± 15 Role-Physical 46 ±43 59 ± 43 13 ± 29 Bodily pain 52 ± 28 67 ± 31 15 ± 21 General Health 47± 17 59 ± 24 12 ± 13 Vitality 46 ± 20 57 ± 21 11 ± 19 Social Function 63± 31 70 ± 26  7 ± 39 Role-Emotional 64 ± 46 90 ± 20 26 ± 57 MentalHealth 70 ± 15 79 ± 13  9 ± 14

[0037] TABLE 7 The Physical Component Summary (PCS) and Mental ComponentSummary (MCS) from 14 Subjects with Inflammation-Related ConditionsBefore and After Intervention with Composition 1. Physical ComponentMental Component Summary Summary (PCS) (MCS) Patient Initial FinalInitial Final Code Major Symptoms Weeks Score Score Change Score ScoreChange 421 Rheumatoid 3 32 19 −13 48 58 10 arthritis 395 Rheumatoid 6 3352 20 59 46 −13 arthritis 235 Rheumatoid 7 50 53 2.8 47 55 8.1 arthritis298 Rheumatoid 7 13 15 2.5 62 58 −3.3 arthritis 370 Rheumatoid 9 45 549.1 21 52 32 arthritis 170 Psoriatic 8 18 12 −6.0 60 67 6.4 arthritis299 Asthma 9 43 39 −3.9 34 47 13 389 Chronic 9 40 40 0.0 31 45 14urticaria 134 Colitis 8 36 39 2.8 42 52 10 430 Inflammatory 9 55 57 1.952 57 4.8 bowel disease  52 Inflammatory 9 41 57 16 54 43 −11 boweldisease 571 Inflammatory 8 40 49 8.9 49 42 −6.9 bowel disease 462Inflammatory 5 29 35 6.2 46 49 2.7 bowel disease  41 Inflammatory 7 4951 1.6 33 59 26 bowel disease  44 Inflammatory 10  56 38 −18 54 59 5.0bowel disease Ave 8 ± 2 39 ± 13 41 ± 15 2.0 ± 10 46 ± 12 53 ± 7.4 6.3 ±13 (Sd)

EXAMPLE 2 Antioxidant Properties of Curcumin, Quercetin and Rosemary

[0038] In the inflammatory state, the potential for a positive feed-backloop exists in oxidative stress induces the production of cytokineswhich then have the potential to increase the risk of further oxidativedamage (Reilly, MP et at, J. Nutr. 128: 434S-438SConner, EM et al,Nutrition 12:274-277 (1996); Baeurle, PA and T Henkel, Annu. rev.Immunol. 12: 141-179(1994); Weiss, SJ, New England J Med. 320: 365-376(1989). One method of interrupting this vicious circle involves the useof antioxidants ( Jacob,RA, Nutr. Res. 15: 755-766 (1995); Halliwell, B,Nutr. Rev. 52: 253-265(1994); Suzuki, YJ et al, Biochem. Biophys. Res.Commun. 189: 1709-1715(1992)). Several phytonutrients possessingantioxidant activity have been utilized in an attempt to intervene inthis cyclic process (Sato, M et al, J. Rheumatology 24: 1680-1684(1997); Skaper, SD et al, Free Radical Biol.Med. 22: 669-678 (1997);Shoskes, DA, Transplantation. 66: 147-152 (1998);Chan, MM et al, Canc.Lett. 96:23-29 (1995)).

[0039] Bioflavonoids, such as quercetin (Rice-Evans, CA et al, FreeRadical Biol.Med. 20: 933-956 (1996), ferulic acid-derivatives such ascurcumin (Sreejayan, N and MNA Rao, Arzneim. Forsch./Drug Res. 46:169-171(1996) and camosic acid derivatives from rosemary (Richheimer, SLet al, JAOCS 73: 507-514 (1996) have all been demonstrated to possesspotent antioxidant activity in vitro which is reflected in theirclinical applications. The present example demonstrates the synergisticantioxidant activity of components of the dietary supplements andmedical foods of the present invention.

[0040] Free radicals are defined as “any [molecular] species capable ofindependent existence that contains one or more unpaired electrons.”(Halliwell D, Gutteridge JMC. Free Radicals in Biology and Medicine. 2nded. Oxford: Clarendon Press; pp. 10-14, (1989)). The tendency to fillmolecular or atomic orbitals by forming electron pairs is the basis offree radical reactivity. The reactive nature of oxygen containing freeradicals explains their tendency to destroy biological molecules.

[0041] Perhaps the classic example of free radical damage is that oflipid peroxidation. The reaction can be initiated by hydroxyl radicalgenerated by the reaction of ferrous ion with hydrogen peroxide (Fentonreaction) summarized below. The loss of an electron (accompanied byproton, H⁺) by the lipid (LH), a typical oxidation reaction, produces asecond radical (L^(•)) as one of the reaction products:

LH+^(•)OH→L^(•)+H₂O (chain initiation by ^(•)OH)

L^(•)+O₂→LOO^(•)

LOO^(•)+LH→L^(•)+LOOH (chain propagation)

[0042] It is apparent that without a mechanism to break this chain ofevents, the reaction could easily spiral out of control. In the case oflipid peroxidation, the reactions of vitamins E and C effectively quenchthe reaction initiated by a lone hydroxyl radical. Rather than reactingwith an additional membrane lipid, an electron is transferred from thelipid peroxyl radical to a nearby tocopherol molecule (E), thusgenerating the tocopheryl radical. The return of the vitamin to thereduced state is accomplished by reaction with ascorbic acid.

[0043] A number of phytonutrients not commonly considered essential forhealth also have the capacity to quench oxygen radical mediatedreactions. Quercetin, curcumin and the rosemary diterpenes, carnosol andcarnosic acid have been studied in this regard (Cuvelier, M-E et al.,JAOCS 73: 645-652 (1996); Richheimer, SL et al. 1996 JAOCS 73: 507-514(1996); Sreejayan, N and M. N. A. Rao., Arzneim.-Forsch/Drug Res. 46:169-171 (1996); Haenen, G. R. M. M. et al., Biochem. Biophys. Res.Comm., 236: 591-593 (1997); Chan, M. M.-y et al., Canc. Lett. 96: 23-29(1995); Jovanovic, SV et al., J. Am Chem Soc. 116: 4846-4851 (1994);Guo, C. et al., J. Agric. Food Chem. 45: 1781-1796 (1997); Rice-Evans,CA et al., Free Rad. Biol. Med 20: 933- 956 (1996).

[0044] The results reported in the present example demonstrate that amixture containing quercetin, curcumin and rosemary extract actsynergistically in vitro. That is to say, the antioxidant activity ofthe mixture is greater than that which would be predicted based on theindividual bioactivities.

[0045] Method: In order to determine the antioxidant capacity of thesubject phytonutrients, the ORAC assay (Cao, G et al., Free Rad. Biol.Med. 14: 303-311(1989)) was utilized. This simple procedure relies onthe fact that peroxyl radicals will quench the fluorescence ofβ-phycoerythrin (β-PE) The addition of an antioxidant capable ofscavenging these radicals is able to inhibit fluorescence quenching.Fluorescence is monitored as a function of time and the extent ofquenching and its inhibition can be determined by calculating the areaunder the curve (AUC).

[0046] A typical reaction will contain 1.67×10⁻⁸ M β-PE in phosphatebuffer and 3 ×10⁻³ M 2,2′-azobis(2-amidinopropane)dihydochloride (AAPH)as well as test material. The reaction is initiated by the addition ofthe peroxyl-radical generating reagent AAPH. Fluorescence (λ_(excit)=540nm; λ_(emis)=565 nm) is measured at one minute intervals and the AUC isdetermined. The difference, or net protection, is equal toAUC_(sample)−AUC_(blank), and represents the antioxidant capacity of thesample. This difference is compared to a standard sample (1 μM finalconcentration) of the water soluble vitamin E analog, Trolox, and theresult is expressed in ORAC units. Where one ORAC unit (U) is defined asthe net protection provided by 1 nmol/ml Trolox (i.e., 1 μM). Thereaction shows remarkable linearity for a variety of antioxidants (Caoet al, 1993). The final results are normalized to Trolox on a weightbasis.

units=(AUC/μg)_(test)/(AUC/μg)_(trolox).

[0047] To generate the data set forth in the present example, sampleswere prepared in acetonitrile, sometimes with the aid of sonication tofacilitate dissolution. One to five μl of sample was added to each 3 mlcuvette, the reaction initiated with AAPH and fluorescence monitoreduntil the quenching was complete. The predicted value for the mixtureswas calculated by using the following equation:

U _(pred) =f _(q) U _(q) +f _(c) U _(c) +f _(r) U _(r)

[0048] where f_(q), f_(c) and f_(r) represent the weight percent andU_(q), U_(c), U_(r) is the activity of the pure ingredient forquercetin, curcumin and rosemary respectively.

[0049] Tables 8 and 9 show the antioxidant properties of curcumin,quercetin and rosemary, alone or in combination, as measured using theORAC assay. The antioxidant properties of pure samples of curcumin,quercetin, rosemary and Trolox were individually assayed and the resultsare set forth in Table 8. The antioxidant properties of mixtures ofcurcumin, quercetin and rosemary were assayed and the observed valueswere compared to the predicted values, as set forth in Table 9. Thepredicted values were determined by adding the individually determinedvalues (set forth in Table 8) for each of the components of the mixture.The observed values were greater than the predicted values for eachcombination of: rosemary plus curcumin; rosemary plus quercetin, androsemary plus curcumin and quercetin. These data demonstrate thatrosemary interacts synergistically with curcumin and quercetin in the invitro ORAC assay. Additionally, as shown in Table 9, this synergisticeffect was also observed when Composition 1 (having the composition setforth in Table 3) was assayed using the ORAC assay. TABLE 8 ORACActivity of Pure Samples of Curcumin, Quercetin, Rosemary and TroloxPercent of Sample Tested (by weight) AUC/μg ORAC curcumin quercetinrosemary Trolox mean sd units (U) 100% 15.93 3.7 1.79 100% 14.45 1.671.62 100% 4.79 1.14 0.54 100% 8.9 1.45 1.00

[0050] TABLE 9 ORAC activity of combinations of curcumin, quercetin androsemary Grams in Mixture Fraction by Weight AUC/μg Units ORAC Unitcurcumin quercetin rosemary curcumin quercetin rosemary mean s.d. pred.obs. 25.2 24.9 0.503 0.497 15.47 4.82 1.71 1.74 33.9 16.1 0.678 0.32219.47 6.1 1.39 2.19 33.8 16.3 0.675 0.325 15.68 8.72 1.27 1.76 20.3 9.720.1 0.405 0.194 0.401 21.02 1.33 1.26 2.36 Composition 1 0.004 0.0040.002 1.27 3.17 0.01 0.05

[0051] While the preferred embodiment of the invention has beenillustrated and described, it will be appreciated that various changescan be made therein without departing from the spirit and scope of theinvention.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:
 1. A dietary supplementcomprising rosemary, curcumin and and at least one additional componentselected from the group consisting of quercetin and rutin, said dietarysupplement compounded for the amelioration of an inflammation-relateddisease.
 2. The dietary supplement of claim 1 comprising rosemary,curcumin and quercetin.
 3. The dietary supplement of claim 1 comprisingrosemary, curcumin and rutin.
 4. The dietary supplement of claim 1comprising rosemary, curcumin, quercetin and rutin.
 5. The dietarysupplement of claim 1 further comprising at least one additionalcomponent selected from the group consisting of limonene, hesperidin andginger.
 6. The dietary supplement of claim 1 further comprising a traceelement selected from the group consisting of zinc, manganese andselenium.
 7. The dietary supplement of claim 1 further comprising avitamin.
 8. The dietary supplement of claim 1 further comprising anon-vitamin antioxidant.
 9. The dietary supplement of claim 2 whereinthe supplement is compounded in a daily dose comprising rosemary presentin an amount of from about 180 milligrams to about 220 milligrams,curcumin present in an amount of from about 360 milligrams to about 440milligrams and quercetin present in an amount of from about 360milligrams to about 440 milligrams.
 10. The dietary supplement of claim3 wherein the supplement is compounded in a daily dose comprisingrosemary present in an amount of from about 180 milligrams to about 220milligrams, curcumin present in an amount of from about 360 milligramsto about 440 milligrams and rutin present in an amount of from about 360milligrams to about 440 milligrams.
 11. The dietary supplement of claim4 wherein the supplement is compounded in a daily dose comprisingrosemary present in an amount of from about 180 milligrams to about 220milligrams, curcumin present in an amount of from about 360 milligramsto about 440 milligrams, quercetin present in an amount of from about360 milligrams to about 440 milligrams and rutin present in an amount offrom about 360 milligrams to about 440 milligrams.
 12. A medical foodcomprising rosemary, at least one macronutrient selected from the groupconsisting of protein, carbohydrate and fat, and at least one member ofthe group consisting of quercetin, curcumin and rutin, said medical foodcompounded for the amelioration of an inflammation-related disease. 13.The medical food of claim 12 comprising rosemary and curcumin.
 14. Themedical food of claim 12 comprising rosemary and quercetin.
 15. Themedical food of claim 12 comprising rosemary, curcumin and quercetin.16. The medical food of claim 12 further comprising a vitamin and anon-vitamin antioxidant.
 17. The medical food of claim 12 furthercomprising limonene, hesperidin and ginger.
 18. The medical food ofclaim 12 wherein the protein is substantially gluten free.
 19. Themedical food of claim 18 wherein the protein is a hypoallergenic riceprotein extract.
 20. The medical food of claim 12 wherein thecarbohydrate is a member of the group consisting of rice fiber, ricebran, rice syrup and rice flour.
 21. The medical food of claim 12wherein the fat comprises at least one medium chain triglyceride.
 22. Amethod for treating an inflammation-related disease comprisingadministering to a person suffering from an inflammation-related diseasean effective amount of a dietary supplement comprising rosemary and atleast one additional component selected from the group consisting ofquercetin, curcumin and rutin.
 23. The method of claim 22 wherein thedietary supplement comprises rosemary and curcumin.
 24. The method ofclaim 22 wherein the dietary supplement comprises rosemary andquercetin.
 25. The method of claim 22 wherein the dietary supplementcomprises rosemary, curcumin and quercetin.
 26. The method of claim 22wherein the dietary supplement further comprises limonene, hesperidinand ginger.
 27. The method of claim 23 wherein the dietary supplement iscompounded in a daily dose comprising rosemary present in an amount offrom about 180 milligrams to about 220 milligrams and curcumin presentin an amount of from about 360 milligrams to about 440 milligrams. 28.The method of claim 24 wherein the dietary supplement is compounded in adaily dose comprising rosemary present in an amount of from about 180milligrams to about 220 milligrams and quercetin present in an amount offrom about 360 milligrams to about 440 milligrams.
 29. The method ofclaim 25 wherein the dietary supplement is compounded in a daily dosecomprising rosemary present in an amount of from about 180 milligrams toabout 220 milligrams, curcumin present in an amount of from about 360milligrams to about 440 milligrams and quercetin present in an amount offrom about 360 milligrams to about 440 milligrams.
 30. A method fortreating an inflammation-related disease comprising administering to aperson suffering from an inflammation-related disease an effectiveamount of a medical food comprising rosemary, at least one macronutrientselected from the group consisting of protein, carbohydrate and fat, andat least one additional component selected from the group consisting ofquercetin, curcumin and rutin.
 31. The method of claim 30 wherein themedical food comprises rosemary and curcumin.
 32. The method of claim 30wherein the medical food comprises rosemary and quercetin.
 33. Themethod of claim 30 wherein the medical food comprises rosemary, curcuminand quercetin.
 34. The method of claim 30 wherein the medical foodfurther comprises limonene, hesperidin and ginger.
 35. The method ofclaim 31 wherein the medical food is compounded in a daily dosecomprising rosemary present in an amount of from about 180 milligrams toabout 220 milligrams and curcumin present in an amount of from about 360milligrams to about 440 milligrams.
 36. The method of claim 32 whereinthe medical food is compounded in a daily dose comprising rosemarypresent in an amount of from about 180 milligrams to about 220milligrams and quercetin present in an amount of from about 360milligrams to about 440 milligrams.
 37. The method of claim 32 whereinthe medical food is compounded in a daily dose comprising rosemarypresent in an amount of from about 180 milligrams to about 220milligrams, curcumin present in an amount of from about 360 milligramsto about 440 milligrams and quercetin present in an amount of from about360 milligrams to about 440 milligrams.
 38. The method of claim 30wherein the protein is a hypoallergenic rice protein.
 39. A dietarysupplement comprising rosemary, curcumin and at least one additionalcomponent selected from the group consisting of quercetin, rutin,limonene, hesperidin and ginger, said dietary supplement compounded forthe amelioration of an inflammation-related disease.
 40. A medical foodcomprising rosemary, at least one macronutrient selected from the groupconsisting of protein, carbohydrate and fat, and at least one additionalcomponent selected from the group consisting of quercetin, curcumin,rutin, limonene, hesperidin and ginger, said medical food compounded forthe amelioration of an inflammation-related disease.